Linked Life Data

12461746

Source:http://linkedlifedata.com/resource/pubmed/id/12461746

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-12-3
pubmed:abstractText
Methylation of the MLH1 promoter region has been suggested to be a principal mechanism of gene inactivation in sporadic microsatellite instability (MSI)-positive colorectal carcinoma. Recently, we have shown a novel methylation profile of the MLH1 promoter region (i.e., full, partial, and no methylation), among which full methylation was strongly associated with MSI. In this study, to confirm whether methylation requires the involvement of both alleles, we studied the MLH1 promoter region concerning the methylation profile and allelic loss. Furthermore, we studied correlations of methylation profiles with genetic alternations such as loss of heterozygosity (LOH) of the TP53 locus and KRAS mutation. Eighty-eight tumors were classified as full (n = 14), partial (n = 26), and no methylation (n = 48). Full methylation was observed in 78% (14/18) of high-frequency MSI, in which all CpG sites in the promoter region were methylated. Full methylation differed significantly from partial methylation regarding absence of TP53 LOH (0/12) and KRAS mutation (0/14). In cases with full methylation, we could show biallelic methylation by use of a single-base nucleotide polymorphism in the promoter. However, this did not accompany LOH of the MLH1 locus. In contrast, there were no significant differences in molecular features between partial and no methylation, except for low frequencies of LOH of the MLH1 locus (P = 0.02). In conclusion, biallelic extensive methylation of the MLH1 promoter region plays a significant role in gene inactivation and is independent of KRAS mutation and TP53 LOH.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1045-2257
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-25
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12461746-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12461746-Age of Onset, pubmed-meshheading:12461746-Aged, pubmed-meshheading:12461746-Carrier Proteins, pubmed-meshheading:12461746-Colorectal Neoplasms, pubmed-meshheading:12461746-DNA, Neoplasm, pubmed-meshheading:12461746-DNA Methylation, pubmed-meshheading:12461746-Female, pubmed-meshheading:12461746-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12461746-Gene Silencing, pubmed-meshheading:12461746-Genes, p53, pubmed-meshheading:12461746-Humans, pubmed-meshheading:12461746-Loss of Heterozygosity, pubmed-meshheading:12461746-Male, pubmed-meshheading:12461746-Middle Aged, pubmed-meshheading:12461746-Mutation, pubmed-meshheading:12461746-Neoplasm Proteins, pubmed-meshheading:12461746-Nuclear Proteins, pubmed-meshheading:12461746-Promoter Regions, Genetic, pubmed-meshheading:12461746-Proto-Oncogene Proteins, pubmed-meshheading:12461746-ras Proteins
pubmed:year
2003
pubmed:articleTitle
Methylation profile of the MLH1 promoter region and their relationship to colorectal carcinogenesis.
pubmed:affiliation
Department of Surgery, Jichi Medical School, Tochigi, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't